Warfarin with statins

An interaction with warfarin with resulting acute rhabdomyolysis has been observed in a patient taking simvastatin (59). This has not been observed with other statins. 

Pharmacological studies of the etfeet of statins on warfarin are summarised in Table 12.6 , (p.449), and ease reports of interactions between statins and coumarins are summarised in Table 12.7 , (p.451). An early report, from the first 7 months after lovastatin became available in the USA, notes that the manufacturers had reeeived 10 spontaneous reports of bleeding and/or increased prothrombin times in patients taking warfarin with lovastatin. ... 

The fibrates potentiate the actions of the coumarin anticoagulants, such as warfarin, so care should be taken to reduce the dose of simultaneously administered anticoagulants, and plasma prothrombin should be frequently measured until the level stabilizes. As mentioned earlier, great care should be given to combining a statin with a fibrate, since this combination may increase the risk of myositis and perhaps rhabdomyolysis. Table 23.4 summarizes major interactions of drugs that lower cholesterol. 

Fluvastatin may increase warfarin toxicity because both compete with P450 2C9 for metabolism. Cerivastatin can cause fatal rhabdomyolysis risk with other statins unclear. 

Interactions of statins with warfarin, resulting in an increased bleeding tendency, have been reported (51), including interactions of anticoagulants with both lovastatin (51) and fluvastatin (89). 

STATINS ANTICOAGULANTS-ORAL Possible t anticoagulant effect with fluvastatin and simvastatin Uncertain possibly due to inhibition of CYP2C9-mediated metabolism of warfarin Monitor INR closely... 

Clinically important, potentially hazardous interactions with dicumarol, ezetimibe, lovastatin, nicotinic acid, statins, warfarin... 

Clinically important, potentially hazardous interactions with atorvastatin, bexarotene, cyclosporine, dicumarol, ezetimibe, fluvastatin, interferon alfa, lovastatin, nicotinic acid, pioglitazone, pravastatin, repaglinide, rosuvastatin, roxithromycin, simvastatin, statins, warfarin... 

Following Ml, all patients, in the absence of contraindications, should receive indefinite therapy with aspirin, a 8-blocker and an angiotensin-converting enzyme (ACE) inhibitor for secondary prevention of death, stroke, and recurrent infarction. Most patients will receive a statin to reduce low-density lipoprotein cholesterol to less than 70 to 100 mg/dL. Anticoagulation with warfarin should be considered for patients at high risk of death, reinfarction, or stroke. 

Some imidazoles (miconazole, fluconazole) are known to interact with oral hypogly-caemic drugs (Chapter 6) by enhancing their activity and they may increase the risk of myopathy with lipid-lowering drugs statins (Chapter 4). Some imidazoles enhance the anticoagulant properties of warfarin. 

The use of statins and probably fibrates should be suspended during daptomycin use because of the possible increased risk of muscle toxicity. Daptomycin does not appear to interact with warfarin, but its use may result in falsely elevated prothrombin times. NSAIDs may reduce daptomycin excretion and concurrent use may increase the risks of renal impairment... 

Studies have suggested that fluvastatin and rosuvastatin can increase warfarin levels and/or effects. Other studies with atorvas-tatin, lovastatin, pravastatin, and simvastatin suggest that they do not usually significantly alter the effects of warfarin, although cases of bleeding have been seen when these statins were given with coumarins and fluindione. 

Herman D, LocateUi I, Grabnar I, Petemel P, Stegnar M, Lainscak M, Mrhar A, Breskvar K, Dolzan V. The influence of co-treatment with carbamazepine, amiodarone and statins on warfarin metabolism and maintenance dose. EurJ Clin Pharmacol (2006) 62,291-6. 

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